ATP-stimulated smooth muscle cell proliferation requires independent ERK and PI3K signaling pathways

• Published in: American journal of physiology. Heart and circulatory physiology 1998-10, Vol.275 (4), p.H1209-H1215
• Main Authors: Wilden, Peter A, Agazie, Yehenew M, Kaufman, Rebecca, Halenda, Stephen P
• Format: Article
• Language: English
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.1998.275.4.h1209

1  Department of Pharmacology, 2  Molecular Biology Program, and 3  Food for the 21st Century Nutrition Program, University of Missouri School of Medicine, Columbia, Missouri 65212 Vascular smooth muscle cells respond to the purinergic agonist ATP by increasing intracellular calcium concentration and increasing the rate of cell proliferation. In many cells the extracellular signal-regulated kinase (ERK) cascade plays an important role in cellular proliferation. We have studied the effect of extracellular ATP on ERK activation and cell proliferation. ATP binding to a UTP-sensitive P2Y nucleotide receptor activates ERK1/ERK2 in a time- and dose-dependent manner in coronary artery smooth muscle cells (CASMC). ATP-induced activation of ERK1/ERK2 is dependent on the dual-specificity kinase mitogen-activated protein kinase/ERK kinase (i.e., MEK) but independent of phosphatidylinositol 3-kinase (PI3K) activity. We provide evidence that both ERK1/ERK2 and PI3K activities are required for CASMC proliferation. Thus ATP-stimulation of CASMC proliferation requires independent activation of both the ERK and PI3K signaling pathways. mitogen-activated protein kinase/extracellular signal-regulated kinase; platelet-derived growth factor; P2 nucleotide receptor; signal transduction; G protein-coupled receptor